This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The focus of the research proposed herein, a renewal of CHE030089N, is to apply modern quantum chemical methods to the elucidation of molecular mechanisms of organic chemical reactions that are used in the synthesis and biosynthesis of polycyclic organic molecules. During this award period, we will concentrate on two subprojects: project 1 (continued from the previous grant period) cation-promoted polycyclization reactions involved in biosyntheses of terpene natural products;project 2 (continued from the previous grant period) pericyclic reactions used in the synthesis of complex cyclic molecules. These investigations should allow us to answer many long-standing questions about the relative importance of preorganization and encapsulation, conjugation, hyperconjugation and homoconjugation, transition metal intervention, electrostatic interactions, hydrogen bonds, and hydrophobic forces in controlling cyclization rates and regio- and stereoselectivities, thus providing important insights into the mechanisms of biosynthetic and synthetic cyclization reactions. Our ultimate goal is to define the specific factors responsible for the efficiency of these transformations, thereby compiling sets of design principles for use in creating new synthetic reactions.